Diabetes has reached epidemic proportions worldwide and most individuals with type 2 diabetes are obese. Therefore, there is a pressing need to carefully evaluate the impact of obesity on the efficacy of all diabetes therapies. Previously, obesity has been shown to adversely affect the efficacy of oral antidiabetic drugs; however, less is known about the impact of obesity on the properties of insulin and its analogues. As patients near target HbA1c, the more postprandial hyperglycaemia contributes to overall glycaemic control; thus, mealtime insulin, often supplied by a rapid-acting insulin analogue (RAI), becomes of increasing importance. As glycaemic targets set by professional bodies become lower and poor glycaemic control becomes increasingly less acceptable, earlier addition of RAIs to patients’ treatment regimens may be required to meet these targets. However, in clinical practice, multiple barriers have challenged the acceptance and effective use of insulin therapy, including concern that it may cause weight gain. RAIs should ideally maintain their rapid-acting pharmacokinetic (PK) and pharmacodynamic (PD) profiles, irrespective of subcutaneous body fat, skin thickness and body mass index, in order to effectively meet intensive treatment goals. For example, initial PK/PD data with insulin glulisine in obese individuals suggest that this RAI may maintain its rapid-acting profile better than insulin lispro in the first 2 hours post-injection. However, data are preliminary and a thorough analysis of the impact of obesity on all RAIs in type 2 diabetes is warranted. This review focuses on the potential impact of obesity on RAIs and presents an overview of investigations in this area.